A Novel Acetaminophen Soft-Chew Formulation Produced via Hot-Melt Extrusion with In-line Near-Infrared Monitoring as a Process Analytical Technology Tool.

ABSTRACT

Patients who suffer from dysphagia have difficulty in swallowing hard tablets and capsules; hence, gelatin-based soft-chew dosages are used as an alternative and novel drug delivery approach to overcome this problem. However, the conventional method of producing gelatin-based soft-chew dosages has many potential issues. The objective of this study was to use glycerol and the hot-melt extrusion technique to address potential issues and optimize the formulation. Gelatin, acetaminophen, saccharin, xylitol, and sodium chloride and six different ratios of water and glycerol were used in the seven formulations. Extrusion process temperature of formulations 1-6 and formulation 7 were 90°C and 140°C, respectively. Near-infrared spectra were collected during extrusion to monitor quality consistency. Scanning electron microscopic images of the cross-section of the soft-chew dosages were recorded. Differential scanning calorimetry (DSC) was used to characterize the crystal states of each formulation. Texture profile analysis was used to evaluate the physical properties of the tablets. In vitro drug release characteristics were studied. A 45-day stability study was carried out to evaluate the stability of each formulation. Near-infrared spectra showed that formulations 1-6 were uniform while formulation 7 was not. From the DSC results, formulations 1 and 2 showed crystallinity of acetaminophen. Formulation 5 displayed the desired physical and chemical stability in texture profile analysis and in the in vitro drug release studies. By using glycerol and hot-melt extrusion, the potential issues of conventional methods were successfully addressed.